Mechanism Of Action Of Pu-erh Tea Reduces The Damage Of Chemotherapy In Normal Cells By Guisiqian

The cancer was called one of the five human disease hazards by the World Health Organization.There are many ways for the treatment of cancer,and the chemotherapy is more effective treatment method.Since the different between cancer cells and normal cells is that the growth of cells,so most of the treatment principle of anticancer drugs is often damaged the mechanism of cell division of cancer cells,to inhibit the growth of cancer cells.Such as inhibit the DNA replication,damage the DNA structure or prevent chromosome segregation.Most chemotherapy drugs are not specificial,it will also kill the cell division in normal cells,which damage the healthy tissue which need the division in order to maintain normal function.These side effects of chemotherapy drugs decline the efficiency and quality,thus affecting the survival rate of patients,and therefore the American Society of Clinical Oncology proposed looking for protective agents to reduce the toxicity of chemotherapy in normal cells.Doxorubicin is considered to have the greatest therapeutic potential and most effective in mangy chemotherapy drugs,but there are also a lot of the most serious side effects such as heart toxicity,cardiac toxicity in the clinical manifestations of no symptoms to occasional threat to the life of congestive heart failure.It has been reported confirmed dexrazoxane as a protective agent doxorubicin in metastatic breast cancer combined.At present,in addition to western medicine protective agent,can also look for from natural plants in southwest regions where there including Yunnan has a wealth of natural plant ingredients,provides a wealth of resources.Such as the pu-erh tea,our laboratory studies have shown that pu-erh tea can be used as a protective agent inhibits the apoptosis of normal cells induced by doxorubicin.Our previous study which used the method of staining with apoptosis showed:the first with a certain concentration of pu-erh tea treatment wild-type mouse embryonic fibroblasts for 24 hours,and after then adding a certain concentration of doxorubicin into cells for 12 hours,24houers,and then compared to doxorubicin treatment alone effect,the pu-erh tea can reduce the doxorubicin induced cell apoptosis,suggesting that the pu-erh tea may protect normal cells;and with the same experimental method,found the pu-erh tea could increased the sensitivity of the tumor cells p53-/-+ s + ras to doxorubicin and the increased the cell apoptosis.In the study of the mechanism of pu-erh tea,found the pu-erh tea work with doxorubicin together on mouse embryonic fibroblasts reduced the expression of heat shock protein 70,heat shock protein 90,p53 protein,which was increased in doxorubicin handled cells.However,in p53-/-+ s + ras cells,the study found that pu-erh tea had no effect of heat shock protein 90,but heat shock protein 70 expression was reduced a little,indicating that the role of pu-erh tea in tumor cells and normal cells was different.In this paper,explored the mechanism of the protective effect and sensitizing effect of pu-erh tea further more.Treated the wild-type mouse embryonic fibroblasts with the pu-erh tea in the same concentration for 24 hours,then add the same concentration of doxorubicin into cells for 8 hours,compared with doxorubicin alone in cells,found the extent of DNA damage is decreased in cells,and found the DNA damage marker protein γ-H2AX expression was decreased.Meanwhile after pu-erh tea interaction with doxorubicin in the cells using Western blotting method detected the expression of heat shock protein transcription factor HSF1,and then found the expression of HSF1 protein was reduced but increased when the doxorubicin induced,indicating that pu-erh tea can reduce the expression of HSF1 protein.AS known the Sirtl protein can stabilizing the effect of HSF1 protein,then detected the Sirtl protein expression by Western blotting and was found when the pu-erh tea and doxorubicin work together,the expression of Sirtl was reduced,which indicating that the protective effect of pu-erh tea may be by inhibiting Sirtl proteins,then inhibit the expression of HSF1,so that reduces the expression of heat shock proteins.The preliminary data showed the expression of p53 protein may also be reduced due to the reduction of DNA damage,and the reduced heat shock protein expression.In addition to studying the protective mechanisms of pu-erh tea,also further to find the effective components of pu-erh tea,and detected the known ingredient of pu-erh tea,such as caffeine,gallic acid,quercetin.Explored the caffeine,gallic acid quercetin whether could reduce the apoptosis by doxorubicin induced in the mouse embryonic fibroblasts,at last there is no significant protective effect.The paper further study the sensitizing effect of tea,with the same cell tumor of p53-/-+ s + ras cells,but this paper for explore the sensitizing effect results with the previous data Pu-erh tea is different,the paper detection the caspas3 protein expression after the pu-erh tea combinated with doxorubicin work for 24h has not increased significantly,but with AnnxeinV/PI double staining flow cytometry apoptosis results after the pu-erh tea together with doxorubicin treated cells,the death rates increased than single doxorubicin induced cell apoptosis.The two opposite result,you can not clear whether the sensitizing effect of pu-erh tea was determined.But after reducing the concentration of doxorubicin,after the pu-erh tea work together with doxorubicin for 24h,the caspase3 protein expression and AnnxeinV/PI double staining results all can be seen pu-erh tea increased doxorubicin induced cells apoptosis.But the specific mechanism of pu-erh tea is not fully understood,and can be determined the effect of pu-erh tea was related with the decreased expression of mutant p53 protein,HSF1 protein.In conclusion of this paper,the pu-erh tea can be used as protective agents for doxorubicin caused normal cells to apoptotic,and further explored the mechanisms,the results clearly show that pu-erh tea could reduce the DNA damage and DNA damage protein y-H2AX protein expression,also reduced the expression of p53,HSP70,HSP90,HSF1,Sirtl,which induced by doxorubicin.While the sensitizing effect of pu-erh tea may require further validation in different ways,and its role of sensitive was related with the reduced expression of mutant p53 protein and HSF1 proteins.